Pemphigus, herpes gestationis, bullous pemphigoid and dermatitis herpetiformis are blistering skin diseases all of which are associated with so-called auto-immune phenomena. We have identified and characterized serum and in vivo bound antibodies in these diseases. Our efforts have centered around the mechanisms of tissue destruction, ultrastructure, and ultra-structural localization of antibodies. Immunogenetic considerations with regard to HLA associations and the identification of specific B-lymphocyte antigens have provided tools to study the triggering mechanisms involved in the early stages of an abnormal immune response. Another major effort is the study of Langerhans cells in inflammatory and immunologically mediated reactions. We have identified the origin of this cell which probably represents the peripheral most limb of the immune response in the skin and have identified its immunological function both in vivo and in vitro. Identification and functional characterization of alloantigens on epidermal cells and of basement membrane constituents are other integral parts of the overall program. We have identified a unique basement membrane zone antigen in human skin, the bullous pemphigoid antigen, and are currently producing monoclonal antibodies to human skin components.